Purpose: Celecoxib is a selective cyclooxygenase-2 inhibitor widely used in patients with osteoarthritis and rheumatoid arthritis. Recently, nonclinical data on the inhibition of human ether-à-go-go-related gene potassium channels by celecoxib were reported, but there is no compelling evidence for this finding in humans. The aim of this study was to assess the potential effects of celecoxib on cardiac repolarization by conducting a thorough QT study, which was designed in compliance with the related guidelines.
Methods: This randomized, open-label, positive- and negative-controlled, crossover clinical study was conducted in healthy male and female subjects. Each subject received, in 1 of 4 randomly assigned sequences, all of the following 3 interventions: celecoxib 400 mg once daily for 6 days; a single dose of moxifloxacin 400 mg, which served as a positive control to assess the assay sensitivity; and water without any drug, which served as a negative control. Serial 12-lead ECG and blood samples for pharmacokinetic analysis were collected periodically over 24 h. Individually RR-corrected QT intervals (QTcI) and Fridericia method-corrected QT intervals (QTcF) were calculated and evaluated.
Findings: Twenty-eight subjects were allocated to 1 of the 4 intervention sequences. The largest time-matched mean effects of celecoxib on the QTcI and QTcF were <5 ms, and the upper bounds of the 1-sided 95% CIs of those values did not exceed 10 ms. Moreover, none of the subjects had an absolute QTcI value of >450 ms or a change from baseline in QTcI of >60 ms after multiple administrations of celecoxib. The QTcI did not show a positive correlation with celecoxib concentrations in the range up to ~2700 μg/L. The overall effects of moxifloxacin on the QTcI and QTcF were enough to establish assay sensitivity. No serious adverse events were reported, with a total of 11 AEs reported in 8 subjects.
Implications: Celecoxib caused no clinically relevant increase in the QT/QTc interval at the maximum dose level used in current practice settings. ClinicalTrials.gov identifier: NCT03822520.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.clinthera.2019.09.004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sulfonamide-Pyrazole derivatives as next-generation Cyclooxygenase-2 enzyme inhibitors: From molecular design to in vivo efficacy.
Int J Biol Macromol
December 2024
Applied Organic Chemistry Department, National Research Center, Dokki, Cairo 12622, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Canal El Mahmoudia St., Alexandria 21648, Egypt. Electronic address:
The current research focuses on the design and synthesis of celecoxib analogues incorporating sulphonamide pyrazole moieties 4, 5, 6a-e, and 7a-f with the aim of achieving a broad range of COX-2 selectivity in vitro. Among these, compounds 6b-d, 7a, 7e, and 7d exhibited potent inhibition, with IC values ranging between 0.05 and 0.
View Article and Find Full Text PDFCelecoxib paradoxically induces COX-2 expression and astrocyte activation through the ERK/JNK/AP-1 signaling pathway in the cerebral cortex of rats.
Neurochem Int
December 2024
Master and PhD Programs in Pharmacology and Toxicology, School of Medicine, Tzu Chi University, Hualien, Taiwan 970; Department of Pharmacology, School of Medicine, Tzu Chi University, Hualien, Taiwan 970. Electronic address:
Previous studies have shown that celecoxib or NSAID may paradoxically induce cyclooxygenase-2 (COX-2) expression and trigger inflammation-like responses in airway smooth muscle cells and renal mesangial cells. Despite the extensive research on celecoxib, its atypical biological effect on the induction of COX-2 in astroglial cells within the central nervous system (CNS) remains unexplored. In the present study, we investigated the impact of celecoxib on COX-2 and Glial Fibrillary Acidic Protein (GFAP) expression and explored the mechanisms underlying celecoxib-regulated COX-2 expression in cortical astrocytes of rats.
View Article and Find Full Text PDFEffects of fluconazole on the pharmacokinetics of celecoxib and its carboxylic acid metabolite in different CYP2C9 genotypes.
Arch Pharm Res
December 2024
School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
This study aimed to investigate the effects of fluconazole, a moderate inhibitor of CYP2C9 and CYP3A4, on the pharmacokinetics of celecoxib and its carboxylic acid metabolite in different CYP2C9 genotypes. A total of thirty-nine healthy Korean male volunteers were divided into three different CYP2C9 genotype groups (CYP2C9*1/*1, *1/*3 and *3/*3 genotypes) and were enrolled in the celecoxib alone trial, celecoxib with fluconazole trial, or both. In the celecoxib alone trial, participants received a single oral dose of 200 mg celecoxib.
View Article and Find Full Text PDFMacranthoidin B restrains the epithelial-mesenchymal transition through COX-2/PGE pathway in endometriosis.
Front Pharmacol
December 2024
School of Chinese Materia Medica, Chongqing University of Chinese Medicine, Chongqing, China.
Introduction: Macranthoidin B is one of the primary and unique triterpenoid saponin metabolites from Hand. -Mazz, which is used to treat endometriosis (EMS) in traditional Chinese medicine. However, the effect of macranthoidin B remains unknown in EMS.
View Article and Find Full Text PDFNon-steroidal anti-inflammatory drugs (NSAIDs) are popular choices for the mitigation of pain and inflammation; however, they are accompanied by side effects in the gastrointestinal and cardiovascular systems. We compared the effects of naproxen, a traditional NSAID, and celecoxib, a cyclooxygenase - 2 (Cox-2) inhibitor, in humans. Our findings showed a decrease in tryptophan and kynurenine levels in plasma of volunteers treated with naproxen.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!